In a Vilsmeier-Haack reaction, aldehyde or formyl groups can be introduced onto an aromatic ring to yield a formylated-aryl moiety. The reaction entails the formation of a Vilsmeier reagent which then reacts with an aromatic ring of an activated molecule such as a phenol or aromatic amine. The reaction is typically described as a neat process i.e., no solvent is used. Monoformylation occurs rapidly, while the bisformylation reaction has much lower reactivity and occurs more slowly. For example, high purity bisformylation of a triarylamine through a Vilsmeier reaction has been shown to require long reaction periods, such as 96 hours, and excess amounts of the Vilsmeier reagent to obtain adequate conversion. The resulting reaction mixture can be extremely viscous resulting in safety and manufacturing issues.
Solvent-based procedures have been used in manufacturing in order to control the heat of reaction and to provide sufficient agitation to the reaction mixture. Commonly used solvents include toluene, xylene, chlorobenzene, dichlorobenzene, and dichloromethane. Use of these solvents in the reaction mixture generally results in a mixture of mono- and bisformylated products. Complete conversion to the bisformylated product appears to be inhibited by the presence of most solvents, thus requiring vigorous purification techniques in order to isolate a pure bisformylated product.
Methods of forcing the Vilsmeier-Haack reaction to completion i.e., complete bisformylation, include a long reaction time, such as 96 hours; an elevated temperature, and excess Vilsmeier reagent. An elevated temperature, such as from about 90° C. to about 110° C. above the decomposition of the Vilsmeier reagent can result in an intractable black tar that is neither organic nor aqueous soluble possibly due to the decomposition of the reactants. The tar can pose difficulties in using and cleaning the devices and equipment used in the reaction process. An excess of Vilsmeier reagent can be about 5 times the equivalent number of formyl groups being introduced into the organic substrate.
Moreover, the addition of solvents to reduce the viscosity of the mixture appears to inhibit the complete conversion of the triarylamine. U.S. Pat. No. 6,172,264 discloses a process for preparing a poly-formyl-substituted triphenylamine derivative comprising allowing a triphenyamine derivative to react with a Vilsmeier reagent in the presence of toluene and an acid selected from the group consisting of Lewis acids and protonic acids, and then subjecting the reaction product to hydrolysis with an alkaline aqueous solution.